Crosstalk between Peroxisomal Activities and Nrf2 Signaling in Porcine Embryos

Abstract

Melatonin and phytanic acid (PA) are known to be involved in lipid metabolism and β-oxidation, in which peroxisomal activities also significantly participate. In addition, other studies have reported that the nuclear factor-erythroid-derived 2-like 2 (Nrf2 or NFE2L2) signaling pathway mediates lipid metabolism and its subsequent cascades. As these mechanisms are partially involved in porcine oocytes or embryonic development, we hypothesized that the factors governing these mechanisms could be interconnected. Therefore, we aimed to investigate possible crosstalk between peroxisomal activities and Nrf2 signaling in porcine embryos following melatonin and PA treatment. Porcine embryos were cultured for seven days after parthenogenetic activation, and subsequently treated with melatonin and PA, or injected with Pex19-targeted siRNAs. Real-time PCR, immunocytochemistry, and BODIPY staining were used to evaluate peroxisomal activities, Nrf2 signaling, and subsequent lipid metabolism. We found that melatonin/PA treatment enhanced embryonic development, whereas injection with Pex19-targeted siRNAs had the opposite effect. Moreover, melatonin/PA treatment upregulated peroxisomal activities, Nrf2 signaling, lipid metabolism, and mitochondrial membrane potentials, whereas most of these mechanisms were downregulated by Pex19-targeted siRNAs. Therefore, we suggest that there is a connection between the action of melatonin and PA and the Nrf2 signaling pathway and peroxisomal activities, which positively influences porcine embryonic development.

Melatonin and Related Compounds: Antioxidant and Anti-Inflammatory Actions

“…Both melatonin and phytanic acid have a role in this, as well as in the nuclear factor erythroid-derived 2-like 2 (referred to as Nrf2 or NFE2L2) signalling pathway. In a study by Kim et al, the interaction between peroxisomal activity and the Nrf2/NFE2L2 pathway, and the interaction with melatonin combined with phytanic acid in porcine embryos, was investigated [6]. The group used targeted siRNAs to silence the peroxisome biogenesis factor Pex19.…”

NRF2 attenuation aggravates detrimental consequences of metabolic stress on cultured porcine parthenote embryos

“…Therefore, gaining a deeper understanding of cellular responses to conditions that elevate oxidative stress is crucial for developing enhanced culture environments and generating healthy embryos and offspring. Previous studies have suggested that NRF2 serves as a critical mediator of the oxidative stress response in embryos 29 , 35 , 54 . However, the importance and role of NRF2 in porcine embryo development under a metabolically stressful environment has not been characterized through its specific inhibition with RNAi.…”

“…NRF2 has been shown to regulate oxidative stress in granulosa cells under stressful conditions 33 , and this function may involve interactions with miRNAs 34 . Furthermore, NRF2 induces peroxisomal activities in porcine oocytes and embryos 31 , 35 . The NRF2 signaling pathway involves numerous targets and regulates over 600 genes 36 , including more than 200 cytoprotective agents like heme-oxygenase 1 (HO1) and SIRT1.…”

Porcine Follicular Fluid-Derived Exosome: The Pivotal Material for Porcine Oocyte Maturation in Lipid Antioxidant Activity

“…This may be explained by the activation of exosomes during isolation. Xu et al suggested that the isolation process may cause changes in the size, shape, and protein contents of exosomes, affecting their functions and applications in clinical trials [ 38 ]; additionally, a study by Lobb et al showed that the functions of exosomes from human plasma and cell culture supernatant were regulated depending on the isolation methods [ 39 ]. This can be interpreted as isolated exosomes having different properties and better functions than intact exosomes.…”